This application responds to RFA-TW-02-002 "Global Health Research Initiative Program For New Foreign Investigators". The Principal Investigator successfully completed his training under an NIH D43 Program (ITREOH), Number 2 D43 TW00641-06, in May 2001, at Michigan State University (MSU) for a Master's Degree in Epidemiology and research on Balkan Endemic Nephropathy (BEN). The PI returned to his country in May 2001 and presently has an appointment with the National Center of Hygiene, Medical Ecology and Nutrition (NCHMEN), Sofia, Bulgaria. In the NCHMEN, he occupies the position of the Head of Epidemiology Laboratory, and he is entrusted with the task of developing the field of Epidemiology. Currently he continues his research on BEN and publishes extensively. His training at MSU, under NIH 2 D43 TW00641-06, and continuing collaboration with MSU will greatly facilitate his task in developing an epidemiology program (training and research) at the NCHMEN and the greater Sofia, and his BEN research. We propose to conduct research on Balkan Endemic Nephropathy in Vratza district, Bulgaria. BEN is a disease, which affects people only in rural areas in Balkan countries, including Vratza district, Bulgaria. In the region, the disease is still a mystery and risk factors remain putative. There is a need to identify the etiology of the disease in order to possibly prevent its development. BEN runs asymptomatically, and, as a result, it is diagnosed at its latest stages. Diagnostic criteria are not well established. There is a need to identify the clinical development in the early stages of the disease, which will help for timely detection and possibly treatment. The proposed work would provide critical information for early detection and a scientific base for the diagnostic criteria of Balkan Endemic Nephropathy. Through this project, we expect to improve our knowledge about diagnostic criteria and early markers of BEN. Thus, we will contribute to the detection of the disease, which is predominant in women - 2/3 of cases are women. At the environmental level, we will identify whether some natural toxicants present in the environment in the region contribute to the development of BEN, and whether these are associated with any early markers of the disease. The proposed grant would strengthen collaboration between the Principal Investigator and his former U.S. scientific mentors.